IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-61595-3.html
   My bibliography  Save this article

Oral dosing of the nucleoside analog obeldesivir is efficacious against RSV infection in African green monkeys

Author

Listed:
  • Jared Pitts

    (Inc.)

  • J. Lizbeth Reyes Zamora

    (Inc.)

  • Savrina Manhas

    (Inc.)

  • Thomas Aeschbacher

    (Inc.)

  • Josolyn Chan

    (Inc.)

  • Vincent Cutillas

    (Inc.)

  • Varsha Nair

    (Inc.)

  • Nicholas C. Riola

    (Inc.)

  • Arya Vijjapurapu

    (Inc.)

  • Meghan S. Vermillion

    (Lovelace Biomedical Research Institute)

  • Stacey Eng

    (Inc.)

  • Christopher Richards

    (Inc.)

  • Dong Han

    (Inc.)

  • Jason K. Perry

    (Inc.)

  • Subhra Chaudhuri

    (Inc.)

  • Szu-Wen Liu

    (Inc.)

  • Clarissa Martinez

    (Inc.)

  • Nadine Peinovich

    (Inc.)

  • Kai-Hui Sun

    (Inc.)

  • Arthur Cai

    (Inc.)

  • Ross Martin

    (Inc.)

  • Jasmine Moshiri

    (Inc.)

  • Charlotte Hedskog

    (Inc.)

  • Darius Babusis

    (Inc.)

  • Dustin S. Siegel

    (Inc.)

  • Rao Kalla

    (Inc.)

  • Vasanthi Avadhanula

    (Baylor College of Medicine)

  • Pedro A. Piedra

    (Baylor College of Medicine)

  • Kim Stobbelaar

    (University of Antwerp
    University of Antwerp)

  • Peter L. Delputte

    (University of Antwerp
    University of Antwerp)

  • Caleb Marceau

    (Inc.)

  • Roberto Mateo

    (Inc.)

  • Evguenia Maiorova

    (Inc.)

  • Hongmei Mo

    (Inc.)

  • Raju Subramanian

    (Inc.)

  • Richard L. Mackman

    (Inc.)

  • Tomas Cihlar

    (Inc.)

  • Simon P. Fletcher

    (Inc.)

  • John P. Bilello

    (Inc.)

Abstract

Respiratory syncytial virus (RSV) is a significant cause of morbidity and mortality in high-risk populations. Although prophylactic options are available, there are no effective oral therapeutics for RSV infection. Obeldesivir (ODV) is an orally bioavailable prodrug of the nucleoside analog GS-441524, which is converted intracellularly to its active nucleoside triphosphate and inhibits the RSV RNA polymerase. Here we report the potent antiviral activity of ODV against geographically and temporally diverse RSV A and B clinical isolates (EC50: 0.20–0.66 μM). Resistance selection studies with ODV and GS-441524 against RSV identify a single amino acid substitution, I777L, in the L polymerase with reduced susceptibility (3.3-3.8-fold) to ODV and GS-441524, indicating a high barrier for resistance development. In an African green monkey RSV infection model, once-daily oral ODV doses of 30 or 90 mg/kg initiated ~24 hours post-infection significantly reduces log10 viral RNA copies/mL × day area under the curve by 69–92% in the upper and lower respiratory tracts. Together, these preclinical data support the clinical evaluation of ODV for the treatment of RSV infection.

Suggested Citation

  • Jared Pitts & J. Lizbeth Reyes Zamora & Savrina Manhas & Thomas Aeschbacher & Josolyn Chan & Vincent Cutillas & Varsha Nair & Nicholas C. Riola & Arya Vijjapurapu & Meghan S. Vermillion & Stacey Eng &, 2025. "Oral dosing of the nucleoside analog obeldesivir is efficacious against RSV infection in African green monkeys," Nature Communications, Nature, vol. 16(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-61595-3
    DOI: 10.1038/s41467-025-61595-3
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-61595-3
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-025-61595-3?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Dongdong Cao & Yunrong Gao & Zhenhang Chen & Inesh Gooneratne & Claire Roesler & Cristopher Mera & Paul D’Cunha & Anna Antonova & Deepak Katta & Sarah Romanelli & Qi Wang & Samantha Rice & Wesley Lemo, 2024. "Structures of the promoter-bound respiratory syncytial virus polymerase," Nature, Nature, vol. 625(7995), pages 611-617, January.
    2. Sarah J. Butcher & Jonathan M. Grimes & Eugeny V. Makeyev & Dennis H. Bamford & David I. Stuart, 2001. "A mechanism for initiating RNA-dependent RNA polymerization," Nature, Nature, vol. 410(6825), pages 235-240, March.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Fernanda A. Sala & Katja Ditter & Olexandr Dybkov & Henning Urlaub & Hauke S. Hillen, 2025. "Structural basis of Nipah virus RNA synthesis," Nature Communications, Nature, vol. 16(1), pages 1-13, December.
    2. Guobao Li & Tianjiao Du & Jiening Wang & Kaiyue Jie & Zhuolu Ren & Xiaokang Zhang & Long Zhang & Shan Wu & Heng Ru, 2025. "Structural insights into the RNA-dependent RNA polymerase complexes from highly pathogenic Marburg and Ebola viruses," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
    3. Ge Yang & Dong Wang & Bin Liu, 2024. "Structure of the Nipah virus polymerase phosphoprotein complex," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    4. Jin Xie & Mohamed Ouizougun-Oubari & Li Wang & Guanglei Zhai & Daitze Wu & Zhaohu Lin & Manfu Wang & Barbara Ludeke & Xiaodong Yan & Tobias Nilsson & Lu Gao & Xinyi Huang & Rachel Fearns & Shuai Chen, 2024. "Structural basis for dimerization of a paramyxovirus polymerase complex," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    5. Dong Wang & Ge Yang & Bin Liu, 2025. "Structure of the measles virus ternary polymerase complex," Nature Communications, Nature, vol. 16(1), pages 1-15, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-61595-3. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.